Study Finds Cannabinoid-Based Treatments Improved Liver and Metabolic Markers in Animal Model

Cannabinoid-based treatments improved several metabolic and liver-health markers in an animal model of diet-induced metabolic liver disease, reports a study published recently in the International Journal of Molecular Sciences.

Researchers from Curtin University, the University of Western Australia and the University of Parma examined the effects of cannabidiol (CBD), oleoylethanolamide (OEA) and a synthetic compound known as PS318 in mice fed a Western-style diet designed to induce obesity and metabolic liver disease.

After 12 weeks on the diet, mice received two weeks of treatment with the compounds either alone or in combination. According to the study, cannabinoid treatments were associated with significant weight loss, improved fasting blood glucose levels and improvements in several liver-related markers.

CBD and OEA each produced notable reductions in body weight when used alone, while combination treatments generally produced stronger effects. The triple combination of CBD, OEA and PS318 resulted in the greatest average weight loss and the largest reduction in fasting blood glucose.

The study also found improvements in liver pathology. CBD treatment significantly reduced hepatocyte ballooning, a marker of liver cell injury, while the triple combination also produced significant reductions in ballooning scores. Several treatments were also associated with reduced liver enzyme levels, including ALT and AST, though not all changes reached statistical significance.

Researchers said the findings suggest that targeting the endocannabinoid system may offer a potential therapeutic approach for metabolic dysfunction-associated steatohepatitis, or MASH, a more severe form of fatty liver disease. They noted that CBD may help by modulating GPR55, while OEA and PS318 may act through pathways involving GPR119 and the gut-liver axis.

However, the authors cautioned that the findings are preliminary. The study was conducted in mice, lasted just 14 days after disease induction and did not include human validation or long-term safety testing. Researchers said additional studies are needed to determine whether the effects are sustained and whether similar benefits could occur in humans.

The study concludes by stating:

To our knowledge, this is the first study to investigate the therapeutic effects of combination cannabinoid treatment in a mouse model of metabolic liver disease. Targeting the endocannabinoid system, even acute treatment markedly improved metabolic parameters, including significant weight loss, reduced fasting blood glucose, and improved liver condition. The triple cannabinoid combination produced the most pronounced effects, improving markers of hepatic injury and inflammation. Mechanistically, modulation of the LPI/GPR55 and GPR119/incretin axes highlights the therapeutic potential of targeting the gut–liver axis using small-molecule agonists and endogenous bioactive lipids.